EP2054105A1 - Dispositif servant à retirer du fluide à partir du sang chez un patient - Google Patents

Dispositif servant à retirer du fluide à partir du sang chez un patient

Info

Publication number
EP2054105A1
EP2054105A1 EP07811487A EP07811487A EP2054105A1 EP 2054105 A1 EP2054105 A1 EP 2054105A1 EP 07811487 A EP07811487 A EP 07811487A EP 07811487 A EP07811487 A EP 07811487A EP 2054105 A1 EP2054105 A1 EP 2054105A1
Authority
EP
European Patent Office
Prior art keywords
header
fluid
blood
patient
filter
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP07811487A
Other languages
German (de)
English (en)
Other versions
EP2054105B1 (fr
Inventor
Barry A. Solomon
Gregory S. Erman
Frank A. Fazio
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fresenius Medical Care Holdings Inc
Original Assignee
Fresenius Medical Care Holdings Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fresenius Medical Care Holdings Inc filed Critical Fresenius Medical Care Holdings Inc
Publication of EP2054105A1 publication Critical patent/EP2054105A1/fr
Application granted granted Critical
Publication of EP2054105B1 publication Critical patent/EP2054105B1/fr
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A61M1/1678—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes intracorporal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A61M1/1621—Constructional aspects thereof
    • A61M1/1623—Disposition or location of membranes relative to fluids
    • A61M1/1627—Dialyser of the inside perfusion type, i.e. blood flow inside hollow membrane fibres or tubes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3403—Regulation parameters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3403—Regulation parameters
    • A61M1/341—Regulation parameters by measuring the filtrate rate or volume
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/145—Ultrafiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/18—Apparatus therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
    • B01D63/02—Hollow fibre modules
    • B01D63/026—Wafer type modules or flat-surface type modules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/08—Prevention of membrane fouling or of concentration polarisation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3331—Pressure; Flow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2209/00—Ancillary equipment
    • A61M2209/08—Supports for equipment
    • A61M2209/088—Supports for equipment on the body
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B01D2313/10—Specific supply elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B01D2313/12—Specific discharge elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B01D2313/21—Specific headers, end caps

Definitions

  • the present invention relates to filtration devices and methods for continuously treating patients suffering from a condition of fluid overload, retention of excess fluids, or hypervolemia, as may be a result of renal or cardiac disease.
  • the present disclosure also relates to hemodialysis devices for treating people with renal failure.
  • the devices can be worn extracorporeally or surgically implanted into patients.
  • Excessive fluid can accumulate in patients suffering from end stage renal disease (ESRD) or congestive heart failure (CHF).
  • ESRD end stage renal disease
  • CHF congestive heart failure
  • the excess fluid first accumulates in the blood and expands the volume of blood leading to hypertension and places increased stress on the heart. This added stress often leads to heart failure and death.
  • the fluid also can accumulate in the pleural cavities of the lungs leading to shortness of breath. Oxygen uptake in the lungs is reduced as air becomes displaced by water. Again, if this condition is not reversed, death can result.
  • CKD Chronic Kidney Disease
  • ESRD End Stage Renal Disease
  • the fluid accumulates first in the blood where the blood volume can expand by as much as 20%.
  • the fluid then accumulates throughout the body ending up in the extremities such as the ankles, hands, and other tissues as edema (swelling). Volumes as large as 7-10 liters or about 15-20 pounds can commonly accumulate. This causes increased stress on the heart as evidenced by significant increases in blood pressure or hypertension and subsequent heart failure. About 60% of hemodialysis patients have chronic hypertension as defined by the WHO guidelines.
  • This fluid overload volume can only be removed from ESRD patients by direct ultrafiltration or by the ultrafiltration action of a dialysis procedure, generally carried out weekly in three 4 hour sessions.
  • CHF chronic myeloma
  • a progressive deterioration of the heart muscle that leads to an inability to pump enough blood to support the vital organs.
  • fluid retention occurs because the blood perfusion pressure in the kidneys is reduced and the kidneys become inefficient in removing fluid.
  • Ultrafiltration offers an efficient fluid removal without those side effects seen with drugs such as kidney failure and blood pressure drops. Furthermore, ultrafiltration quickly relieves the symptoms of shortness of breath and joint swelling.
  • Ultrafiltration is a process by which blood is exposed (under pressure) to a semi-permeable membrane.
  • the membrane properties dictate that water, salts, and other small molecular weight molecules pass through the membrane, but blood cells, proteins, and other large molecular weight molecules are not separated.
  • the ultrafiltration cartridge is generally made up of a very large number of small diameter hollow fiber membranes.
  • blood is removed from the patient via a catheter placed in an artery or large vein and is pumped into the ultrafiltration cartridge to generate the pressure necessary to carry out the ultrafiltration process.
  • the hollow fibers are arranged so that the blood is perfused through these hollow fiber membranes and the filtered fluid is then removed and discarded, while the treated blood is then returned via another catheter back to the patient.
  • the fluid amount to be removed is generally determined by the amount of weight the dialysis patient has gained since the last dialysis and/or ultrafiltration session. Excessive fluid removal often leads to a significant drop in the patient's blood pressure (hypotension), which can lead to hemodynamic instability and fainting, cardiac arrest, or death.
  • Another drawback of conventional ultrafiltration is the need to use anticoagulants, such as heparin or citrate, to prevent the blood from clotting in conventional ultrafiltration devices.
  • anticoagulants such as heparin or citrate
  • continuous anticoagulation must be utilized at anticoagulant levels sufficient to prevent clots from forming in the device.
  • Prolonged use of anticoagulants presents a significant risk to patients in general because of the possibility of uncontrolled bleeding occurring and particularly to the majority of ESRD patients who are undergoing thrice weekly hemodialysis procedures during which they also receive anticoagulation.
  • the cartridges contain a large number of small diameter hollow fiber membranes, which presents a large contact surface for filtration and toxin clearance. While this large surface area, approximately 1 -2 m 2 (10,000 - 20,000 cm 2 ) is required to achieve the performance characteristics required for a short term (2-6 hr) extracorporeal ultrafiltration session, it exposes the blood to an equally large surface area of foreign material.
  • the small diameter membranes are used to minimize the extracorporeal volume of blood that is required to be used during typical hemodialysis or ultrafiltration.
  • This combination of large numbers of fibers coupled with their small diameters results in an overwhelming surface-to-volume ratio with which the natural coagulation system of the patient must deal.
  • a high level of anticoagulation is required to prevent the blood from clotting in the cartridge. While this anticoagulation is medically acceptable over the relatively short period of the hemodialysis or hemofiltration sessions, long-term chronic use of high doses of anticoagulants is medically unacceptable.
  • continuous use in an extracorporeal circuit of existing dialyzers is generally not possible for more than approximately 48-72 hours.
  • vascular grafts have been largely successful as a long-term blood access conduit in vascular reconstruction surgery. Graft survivals of over 5 years continuous use have been shown with the use of low or no anticoagulants.
  • a 60 cm long coil of 6 mm inner diameter hollow fiber ultrafiltration membrane was implanted into large animals by attaching the device directly to the circulatory system via 6 mm polytetrafluoroethylene (PTFE) vascular grafts as an arterio-venous shunt using the iliac artery and vein.
  • PTFE polytetrafluoroethylene
  • the devices and techniques disclosed herein are designed to address these and other deficiencies of prior art devices and techniques for addressing hypervolemia in ESRD and CHF patients through continuous ambulatory volume control and addressing blood toxicity an renal failure patients through hemodialysis.
  • the present invention provides methods and apparatuses for continuous blood ultrafiltration and/or hemodialysis which are substantially non-thrombogenic.
  • the disclosure further provides ultrafiltration and hemodialysis apparatuses which can be reliably and safely implanted into the blood circulatory system of patients and continuously and automatically remove excess fluid and/or blood toxins, without the use of perfusion pumps or percutaneous access devices.
  • one embodiment of the present invention is an apparatus for removing fluid from the body of a patient.
  • the apparatus includes a first header defining a first flow path with a single inlet and multiple outlets and a second header defining a second flow path having multiple inlets and a single outlet.
  • a filter is in fluid communication with the first header and the second header.
  • a first graft is included for connecting the vascular system of the patient to the single inlet.
  • a second graft is included for connecting the single outlet to the vascular system of the patient.
  • a housing is adapted to collect fluid that passes through the filter.
  • a drain conduit is connected to the housing.
  • Another aspect of an embodiment of the invention includes the first flow path being adapted to uniformly distribute fluid flow in the first flow path, and the second flow path being adapted to uniformly distribute fluid flow in the second flow path.
  • Uniform fluid flow may be achieved by including one or more flow restricting neck regions or necks in the first flow path, the second flow path, or both.
  • the flow restricting neck regions may be located near one or more of the multiple outlets of the first header, one or more of the multiple inlets of the second header, or both.
  • the flow restricting neck regions near the multiple outlets of the first header may be more flow restrictive the closer they are to the single inlet of the first header.
  • the flow restricting neck regions near the multiple inlets of the second header may be more flow restrictive the closer they are to the single outlet of the second header.
  • Uniform fluid flow may also be achieved by having the first flow path progressively bifurcate divergently from the single inlet to the multiple outlets, having the second flow path progressively converging from the multiple inlets to the single outlet, or both.
  • first header and the second header are elongated.
  • the first header, the second header, the filter and the housing are substantially coplanar, and their thickness is about 10 mm or less.
  • the drain conduit may be connected to the bladder of the patient.
  • the patient may then remove the fluid by natural urination.
  • a valve may be adapted to restrict fluid flow through the drain conduit.
  • the valve may be controlled by a sensor and a microprocessor based on physiological parameters of the patient. Alternatively, the valve may be controlled manually.
  • Another embodiment of the present invention includes a first header having a first inlet and multiple outlets and a second header having multiple inlets.
  • a filter is in fluid communication with the first header and the second header.
  • the first header, the second header and the filter define a flow path.
  • the flow path may include one or more neck regions near one or more of the multiple outlets.
  • the flow path may also include one or more neck regions near one or more of the multiple inlets.
  • the filter may include multiple hollow fiber membranes.
  • the filter may be substantially permeable to water and substantially impermeable to blood cells and proteins.
  • a further embodiment of the present invention is an implantable hemoconcentrator for removing fluid from the blood of a patient.
  • the implantable hemoconcentrator includes a first header, a second header, and a filter.
  • the filter is in fluid communication with the first header and the second header.
  • the filter includes a plurality of hollow fiber membranes.
  • the first header, the second header and the filter are adapted to define a flow path that provides substantially uniform flow of blood through each of the hollow fiber membranes with minimal stagnation in the flow of blood.
  • a further embodiment of the present invention is a method for removing fluid from the body of a patient.
  • a fluid removing device is surgically implanted in the patient.
  • the fluid removing device includes a first header defining a first flow path having a first inlet and multiple outlets and one or more necks located near one or more of the multiple outlets.
  • the device also includes a second header with multiple inlets and a second outlet, a filter in fluid communication with the first header and the second header, a first graft for connecting to the vascular system of the patient to the first inlet, a second graft for connecting the second outlet to the vascular system of the patient, a housing adapted to collect fluid that passes through the filter, and a drain conduit to the housing.
  • the first graft is connected to a first blood vessel of the patient, which may be the femoral artery.
  • the second graft is connected to a second blood vessel of. the patient, which may be the femoral vein.
  • the drain conduit is connected to the bladder of the patient.
  • the device may be implanted in a subcutaneous location, such as the retropubic space.
  • the method may also include controlling the volume of fluid removed.
  • Another embodiment of the present invention involves an ultrafiltration device containing a small number of large bore hollow fiber membranes and inlet and outlet distribution elements to evenly distribute and consolidate the fluid flow so as to maximize the efficiency of the device and minimize the disturbance of the blood flow to enable operation of the ultrafiltration device with a minimum of or no anticoagulant.
  • Another aspect of an embodiment of the present invention is an ultrafiltration device adapted for direct implantation into the patient's blood circulatory system incorporating a material suitable to attach (1) the blood inlet of the ultrafiltration device directly to an artery, (2) the bltjodi outlet of the ultrafiltration device directly to a vein, and (3) the filtered fluid outlet of the ultrafiltration device to the bladder of the patient.
  • a further aspect of an embodiment of the present invention is an exemplary ultrafiltration device incorporating a system that controls the removal of excess fluid from the circulatory system based upon a change in a relevant physiological parameter , e.g., blood pressure, blood oncotic pressure, blood osmoality, blood constituent level, blood gas levels (e.g., p ⁇ 2 , pCCh) and combinations thereof.
  • a relevant physiological parameter e.g., blood pressure, blood oncotic pressure, blood osmoality, blood constituent level, blood gas levels (e.g., p ⁇ 2 , pCCh) and combinations thereof.
  • An additional aspect of an embodiment of the present invention is an ultrafiltration device that includes a system to transmit real time diagnostic data.
  • Devices and procedures according the present invention may eliminate or reduce excess fluid and eliminate or reduce the complications associated with hypervolemia. This will help to reduce the incidence of hypertension and associated cardiac disease.
  • the device operates to lower blood pressure and reduce the incidence of pulmonary edema, and allows patients to ingest fluids as needed without the constant concern of controlling and monitoring fluid intake.
  • Such a system is expected to lead to improvements in patient health, quality of life, and patient morbidity and mortality. These improvements may be achieved by slowly and continuously removing excess fluid from patients suffering from hypervolemia.
  • FIG. l is a simplified view of a device according to the present disclosure showing a relatively the small number of relatively large bore hollow fibers and the inlet and outlet bifurcated distribution elements;
  • FIG. 2 is a detailed view of a bifurcated distribution element shown in FIG. 1 according to the present invention
  • FIG. 3 is a simplified view of the filtration device according to the present disclosure showing the bifurcated distribution elements
  • FIG. 4 is an exploded detail view of the bifurcated distribution element according to the present disclosure.
  • FIG. 5 is a simplified view of the device according to the present disclosure showing implanted device in a body by attaching the blood path of the device to an artery or vein and the filtrate path of the device to the bladder and showing the device that controls the amount of fluid removed based on a change in a physiological parameter;
  • FIG. 6 is a simplified view of the device according to the present disclosure showing device attached to the vascular system and a collection bag (in the case of a wearable, extracorporeal embodiment);
  • FIG. 7 is a schematic view of a filter device with the connections desirable to implant it in a body
  • FIG. 8 is a schematic view an embodiment of the filter device that is implantable in a body
  • FIGS. 9-12 are a series of views of an embodiment of the header and flow paths through the header;
  • FIGS. 13 and 14 are views of the flow path of the entire device illustrating necking of the flow path;
  • FIG. 15 is a schematic view of a filter device configured to provide hemodialysis;
  • FIG. 16 is a schematic view of a filter device with exemplary dimensions
  • FIG. 17 is a detailed view of the filter header with exemplary dimensions.
  • FIGs. 18, 19 and 20 are views of the flow velocity of an embodiment illustrating the effect of neck regions on uniformity of flow.
  • FIG. 21 is a graph showing pressure drop versus blood flow rate through an embodiment of the disclosure.
  • FIG. 22 is a graph showing shear forces versus exposure time for embodiments of the disclosure.
  • the invention provides methods and apparatuses for continuous blood ultrafiltration and/or hemodialysis which minimize thrombosis in and caused by the apparatuses.
  • the apparatuses so limit apparatus-related thrombosis via the use of variable diameter and/or bifurcating blood channel designs which assure that the blood constituents are not exposed to undue shear forces, while at the same time minimizing the number of blood flow stagnation points.
  • the apparatuses also use large-bore filter fibers that minimize the processed blood's exposure to any thrombogenic filter surfaces within the apparatuses.
  • the present invention provides devices and methods for the ultrafiltration of water, salts and other small molecular weight molecules from the blood- Blood cells and other large molecular weight molecules like proteins are typically not removed from the blood during this ultrafiltration process.
  • the process takes place by exposing blood, contained in one chamber, under pressure to one side of a semipermeable membrane whereby the small molecules contained in the blood are filtered across the membrane, which is then collected in a second chamber. Once treated, the blood is then returned to the body and the filtrate is then discarded.
  • the present invention also relates to devices that can provide hemofiltration and hemodialysis for both volume control and/or toxin removal within the blood.
  • an ultrafiltration device 10 is comprised of a bundle of hollow fiber membranes 5 contained within a housing 1.
  • the device contains a conduit 2 to form a single blood flow path into the device and a conduit 3 to form a single blood flow path exiting the device and a conduit 4 for the filtered fluid to exit the device.
  • the conduits 2 and 3' may ⁇ be referred to as flow headers.
  • the hollow fiber membranes (tubes) 5 can be made of any biocompatible material used for hemodialysis or hemofiltration membranes to remove toxins and/or fluid. These materials include, but are not limited to, polysulfone, cellulose acetate, polyacrylonitrile, or polymethylmethacrylate.
  • the fabrication of these hollow fiber membranes can be accomplished by any number of known methods used in the manufacturing of medical grade hollow fibers for hemodialysis or hemofiltration devices.
  • the housing and conduits of the device can be made of any biocompatible material including, but not limited to,, polymers like styrene acrylonitrile (SAN), polycarbonate (PC), polymethylmethacrylate (PMMA) 5 polytetraflouroethane (PTFE), polyethylethylketone (PEEK), polydimethylsiloxane (PDMS), polyurethane (PU), or polysulfone (PS) 5 or metals like stainless steel or titanium, or ceramics.
  • SAN styrene acrylonitrile
  • PC polycarbonate
  • PMMA polymethylmethacrylate
  • PTFE polytetraflouroethane
  • PEEK polyethylethylketone
  • PDMS polydimethylsiloxane
  • PU polyurethane
  • the hollow fiber membranes can be sealed into the housing using a variety of biocompatible potting compounds including, for example, polyurethane or epoxy.
  • An embodiment of an ultrafiltration device according to the present invention preferably produces between 0-4 liters of fluid per day (0 - 3 ml/min) which is readily achievable in a device containing high flux hollow fiber membranes having a total membrane surface area of less than 500 cm 2 when operated at an average transmembrane pressure gradient of about 50 ramHg and a blood velocity of approximately 30 cm/sec.
  • the term high flux refers to the (increased) pore size of the filter element. Dialysers can have increased the pore size of the filter element to increase the efficiency of the dialysis treatment.
  • the flux is about 1 ml/min/m /mmhg.
  • the filter surface area is preferably about 3 to about 6% of the membrane filter surface area of hemodialyzers and hemofilters. Accordingly, devices built according to this embodiment may be considerably smaller than that of existing hemodialyzers and hemofilters. With the reduced size improvement it is possible to design a system that is sized for implantation within the body of hypervolemic patients.
  • FIG. 2 illustrates the conduit 2 distribution element of the ultrafiltration device according to an embodiment of the present invention that splits and channels the single incoming flow path of blood into discrete flow paths 6 which flow into the core of the hollow fiber membranes.
  • the conduit 3 (illustrated in FIG. 1) collects and channels the discrete flow paths of blood exiting the hollow fiber membranes into a single exiting flow path.
  • the design of the flow headers of this embodiment of the disclosure is based on the formation of a bifurcated channel network which optimizes the hydrodynamic forces acting on the blood as it passes through the conduit in a manner so as to minimize the disturbance of the blood flow path and to eliminate any stagnation points within the flow path.
  • the header diverges into four different conduits at a pass. See for example, FIG. 4.
  • the diverging fluid paths created at a single stage could be more or fewer than 4.
  • significant to the design of this bifurcated network is the angle of divergence for each successive level of fluid splitting. In doing such, the thrombogenicity of the conduit is kept to a minimum, which then minimizes the amount of anticoagulant that is used to maintain the system clot-free throughout its intended use.
  • the bifurcating header may be constructed in stages where successive stages are aligned to distribute the flow of blood to the filter elements. Bifurcate, as used herein, shall mean to divide or separate into two or more parts or branches.
  • the number of hollow fibers contained within the device housing is significantly lower than the number of hollow fibers generally found in many dialyzers.
  • the present invention also provides larger inner diameters of the hollow fiber membranes, in order to prevent clotting in the long-term use of the device.
  • hollow fiber membranes generally used in existing hemodialyzers or hemofilters are smaller than the currently contemplated preferred embodiment.
  • the number of the hollow fiber membranes is about (approximately) 25 to about 50 hollow fiber membranes.
  • the hollow fiber membranes have an inner diameter of between about 2 to about 7 mm, about 10 to about 15 times that of most hollow fiber membranes incorporated into hemodialyzers and hemofilters.
  • the increased inner diameter of the hollow fiber membranes reduces the surface to volume ratio of the membrane and such reduction of surface to volume ratio provides improved thrombogenicity.
  • the lower surface to volume ratio can also lead to a higher device volume per unit surface area than those devices utilizing smaller diameter hollow fiber membranes.
  • the total membrane surface area that appears to be needed to meet the performance requirements of a device according to one embodiment is about (approximately) 3 to about 6% of that in existing hemodialyzers and hemo filters.
  • the volume per surface area with hollow fibers (even with inner diameters 10 to 15 times that of most hemodialyzers and hemofilters) is less than 20 ml or about 20% that of common hemodialyzers or hemofilters.
  • the discrete flow paths emanating from the flow headers 2, 3 are also aligned with the corresponding hollow fiber membranes 5 so as to form a stepless junction between the conduit and the core of the hollow fiber membrane.
  • conduits 22 are perpendicular to an end face 24 of the header and the fiber membranes are also perpendicular to end face 26 (identified in FIG. 1) of the filter body.
  • a template may be used to precisely align the hollow fibers prior to their being sealed into the housing 1 during the fabrication of the device.
  • each hollow fiber membrane is aligned with a discrete blood flow path so that blood flow in all hollow fiber membranes is uniform and no turbulent flow or boundary layer separation is significantly reduced or eliminated occurs maintaining the low thrombogenicity of the overall device.
  • the housing 1 may have an external shell 30 that contains the filter elements and endplates 32 that secure the filter element in axial alignment with the device.
  • the axis of the filter elements are disposed perpendicular to the endplates.
  • the ultrafiltration device 1 can be modified for implantation directly into the patient by forming a conduit between the inlet of the device and artery 8 using a large bore vascular graft 7 and the outlet of the device and a vein 9 also using a large bore vascular graft 7.
  • the pressure difference between the artery and vein are sufficient to provide the necessary driving force to perfuse the blood through the device and establish a high enough transmembrane pressure to allow the required fluid to be removed from the blood using the small membrane surface area incorporated into the device.
  • the material of the vascular graft can be any material used today for grafts such as polytetraflouroethane (PTFE) or woven Dacron, but the diameter of the graft should be large enough to permit unhindered blood flow to and from the device.
  • the inner diameter of the vascular graft connections is between 2 mm and 7 mm.
  • the connection between the vascular graft and the device should be such that there is essentially a stepless conduit so as to avoid generating turbulence in the blood flow path and maintain a low level of thrombogenicity in the overall device.
  • the filtrate from the device in a fully implanted device can readily be collected in the bladder 11a by connecting a suitable conduit 11 between the filtrate outlet of the device and the bladder.
  • the material of this conduit can be of any biocompatible material including, but not limited to, silicone or polyurethane. Many commercially available nephrostomy "catheters may be used for this purpose.
  • the bladder As the collection site for the filtered fluid, normal urination will periodically remove the fluid from the body and provide for additional capacity for future filtration volumes. Normal urination provides patients with the psychological benefit over use of a urinary bag. However, should the bladder not be functioning in the patient due to chronic atrophy, an external connection via a standard percutaneous catheter can be made between the filtrate outlet of the device and a standard urinary collection bag.
  • One aspect of the invention provides a system to prevent over filtration of the hypervolemic patients.
  • the device is fitted with a control valve 13 on the filtrate outlet of the device. When this valve is closed, no ultrafiltration takes place, but the blood still readily flows through the device maintaining its patency.
  • the valve' is connected to a blood pressure sensor on the blood inlet conduit of the device so that the inlet blood pressure determines the status of the control valve.
  • the filtrate control valve is opened and ultrafiltration of the blood occurs to remove excess fluid.
  • the sensor sends a signal to the filtrate control valve and the valve is closed and the fluid removal terminates.
  • the filtrate valve opens and the ultrafiltration resumes to remove the excess fluid.
  • the physiological parameter that could be monitored to control the device may be lung capacity or volume.
  • blood parameters such as, e.g., blood pressure, blood oncotic pressure, blood osmoality, blood constituent level, and/or blood gas levels (p ⁇ 2, PCO 2 ) can be so monitored.
  • blood pressure e.g., blood pressure, blood oncotic pressure, blood osmoality, blood constituent level, and/or blood gas levels (p ⁇ 2, PCO 2 )
  • other physiological parameters even a combination of parameters, could be used to control the device and thus the volume of fluid in the patient.
  • the ultrafiltration device is attached external to the body in such a fashion as to permit the patient full range of ambulatory motion.
  • the blood inlet of the device 1 is attached to an artery 15 via a percutaneous arterial catheter 17 and the blood outlet of the device is connected to a vein 14 via a percutaneous venous catheter 16.
  • the inherent blood pressure difference between an artery and a vein eliminates the need for an additional blood pump to generate the required blood flow rate and transmembrane pressure difference to establish the ultrafiltration required to alleviate the hypervolemic condition.
  • the filtrate outlet of the device is connected to a standard urinary collection bag 19 via a suitable catheter 18.
  • the filtration volume control system is present.
  • the system includes, but is not limited to, a manual on-off valve, an automatic valve connected to a blood pressure sensor, or a battery controlled mini-pump.
  • Methods to immobilize the external elements in one embodiment include, but are not limited to, attaching the external elements to a vest or belt.
  • the ultrafiltration device is attached to the blood circulatory system of the patient by attaching both the blood inlet and blood outlet of the device to veins 14 via percutaneous venous catheters 16.
  • a blood perfusion pump 20 is used to establish the blood flow rate and transmembrane pressure gradient to achieve the required ultrafiltration performance of the device.
  • the transmembrane pressure gradient can also be achieve through the use of a pump 21 on the filtrate outlet conduit to establish a negative pressure in the filtrate chamber, thus creating a sufficient transmembrane pressure gradient to establish the required ultrafiltration performance of the device.
  • the device can be used with sensors that have the capacity for real time diagnostic data gathering.
  • blood sensors can be disposed in the conduits, e.g., 7, so that various types of parameters may be measured. Some of the physiological parameters that could be measured include blood cell counts, blood pressure, blood oncotic pressure, blood osmoality, blood constituent level, and blood gas levels (pO2, pCO2)or other parameters that can be productively measured within the bloodstream.
  • the diagnostic data that is collected can be used to operate the device, e.g., open a valve to allow the filter to remove water from the bloodstream. Alternatively, the diagnostic data can be used for some other productive collateral benefit such as regulating medicines or machines to enhance patient comfort.
  • FIG. 8 illustrates a schematic view of an embodiment of an ultrafiltration device 100 that is implantable into the body of a person.
  • the embodiment includes an inlet header 110 and a hollow fiber ultrafiltration core 112 and an outlet header 114.
  • the ultrafiltration core 112 is disposed between the inlet and outlet header in a fluid tight manner.
  • the inlet header 110 includes an inlet conduit 116 that forms an attachment point for a graft material 118 from a femoral artery 120.
  • the vascular graft is a 6 mm PTFE graft.
  • a cut is made into the femoral artery and the graft material 118 is attached to the femoral artery 120 at location 122 in a known manner.
  • the headers 110 and 114 may alternately be referred to as manifolds or grooved headers.
  • the outlet header 114 includes an outlet conduit 124 so that a vascular graft 126 may be attached to the outlet header.
  • the vascular graft is a 6 mm PTFE graft.
  • the other side of the graft 126 is attached to a femoral vein 128 at an attachment location 130.
  • the ultrafiltration device 100 is surgically implanted in a subcutaneous location near and above the groin, such as the retropubic space. This allows for shorter vascular grafts 118 'and 126 to connect the ultrafiltration device 100 to the femoral artery 120 and femoral vein 130. In this location the valve 152 can be accessed and adjustments made without penetrating the skin, i.e. extracorporeally (the valve 152 is discussed further below). The surgical procedure can be performed using local anesthesia. The ultrafiltration device 100 can be removed or exchanged in a relatively simple surgical procedure.
  • the hollow fiber ultrafiltration core 112 includes a multiplicity of hollow fibers 140 that extend from the inlet header 110 and the outlet header 114 in a fluid tight manner. That is, blood that leaves the femoral artery 120 at the attachment point 122 and travels through the graft material 118 and into the header 110 will pass through the header into the plurality of hollow fibers 140.
  • the housing protects the hollow fibers and also collects fluid that passes through the wall of the fibers.
  • the hollow fibers are connected to the outlet header 114 in a manner similar to the inlet header and fluid that passes through the fibers into the outlet header can be collected in the outlet header and pass through the graft material 126 and back into the bloodstream through the femoral vein.
  • the housing 142 includes a drain conduit 150 with a valve 152.
  • the valve operates as a safety valve with a manual control so that the device can be properly regulated.
  • the outlet of the drain conduit is configured to drain into the bladder 154.
  • the drain conduit in a preferred form, may be a Filtrate Suprapubic Malecot Bladder Catheter available through Cook Medical, Bloomington, Indiana.
  • the Malecot catheter includes radially expandable distal end to secure the catheter within a bladder. Of course alternative catheters may be used to dispose of the fluid from the device. Additionally, the conduit can be directed outside the body and connected to an ostomy bag.
  • the device 100 is substantially flat and the components of the device are substantially coplanar as shown in FIG. 8 in order to facilitate implantation of the device in the body of a patient.
  • the housing 142 and the ultrafiltration core 112 may be constructed out of flexible materials. This flexibility will permit the device 100 to bend or flex, further facilitating the implantation and maintenance of the device in the body of a patient.
  • the housing 142 may be constructed from substantially inflexible material.
  • FIGS. 9 and 12 illustrate embodiments of the inlet header 110 and outlet header 114.
  • the inlet header 110 and the outlet header 114 are identical, and they are show as such in FIGS. 9-12. If the inlet header 110 and the outlet header 114 are identical this will likely streamline design, manufacture and assembly of embodiments disclosed herein.
  • the inlet header 110 defines a flow path 153 beginning at the inlet conduit 116 which then is split or bifurcated into multiple separate flow passages 156.
  • the separate flow passages 156 connect to the hollow fibers 140.
  • the outlet header 114 defines a flow path 153 beginning at the separate flow passages 156 at the juncture with the hollow fibers 140 and combines or converges the separate flow passages 156 into a single outlet conduit 124.
  • the flow paths 153 defined by the inlet heiader 110 and outlet header 114 may be adapted to optimize the hydrodynamic forces acting on the fluid passing through the flow paths 153.
  • FIG. 12 shows a partial cutaway view illustrating the flow path 153.
  • FIGS. 10 and 11 illustrate the flow paths 153 defined by the headers 110 and 114.
  • the header flow paths 153 are configured to have smoothly diverging/converging conduits.
  • Reference numeral 153 in FIGS. 10 and 11 illustrates the volume of the flow paths 153 themselves.
  • the headers 110 and 114 define the flow path 153.
  • Flow passages 156 are adapted to fit the hollow tubes 140 of the ultrafiltration core 112.
  • the connection preferably is made to be as smooth as possible (without discontinuities) so that the possibility of blood clotting is minimized.
  • the headers 110 and 114 including the corresponding flow paths 153 may be adapted to optimize the hydrodynamic forces acting on the blood as it passes through the flow paths 153 in a ' ma ⁇ ner s'o as to minimize the disturbance of blood flow and to reduce or eliminate any stagnation points within the blood flow.
  • the angle and path of divergence for each flow passage 156 may be adapted to minimize thrombogenicity in blood flow, which eliminates or minimizes the amount of anticoagulant that must be used to maintain the system clot-free throughout its intended use.
  • the flow path includes neck regions or necks, e.g. 170, 172.
  • Neck regions are shown as constrictions or restrictions in the flow passages 156.
  • one or more of the neck regions may be located in the hollow fibers 140, preferably located towards the end of the hollow fibers 140.
  • the neck regions closer to the header inlet conduit 116 and header outlet conduit 124 , e.g. 170, are narrower (i.e., more flow restrictive) than the neck regions, e.g. 172, at the regions further away from the header inlet conduit 116 and header outlet conduit 124.
  • the variation in neck region size may be adapted to provide for more uniform volume of blood flowing through each of the hollow fibers 140, minimize blood flow disturbance, and reduce or eliminate any stagnation points within the blood flow.
  • FIGS. 13 and 14 show an embodiment of the invention with neck regions, e.g. 170, 172, located in the inlet header 110 and the outlet header 114. Alternatively, neck regions could be present only in the inlet header 110 or the outlet header 114. Such an arrangement may require the neck regions to be more constricting as compared to the embodiment with neck regions located in both the inlet header 110 and the outlet header 114.
  • FIG. 15 illustrates a device configured for hemodialysis. Like reference numerals will be used for like elements from FIG. 8 and need not be described here.
  • a fluid conduit 185 is uses to deliver dialysate to the housing 142 so that the filter elements 142 that have blood passing through can remove toxins through a convection gradient across the filter element so that the toxins are removed from the blood into the dialysate and the dialysate fluid removed from the hemodialysis element.
  • FIG. 16 illustrates exemplary dimensions of a device according to the present disclosure.
  • the inlet header 110 has an approximately 6mm inlet and is about (approximately) 75 mm in length.
  • the width is approximately.23 mm.
  • the hollow fiber ultrafiltration core 112 is about 74 mm wide and has a length of about 75 mm.
  • About 32 tubes are disposed in the core and are connected to the inlet and outlet.
  • the outlet header 114 has similar dimensions as the inlet header.
  • the headers have an overall length of approximately 95mm and the inlet/outlet conduit is approximately 6mm in diameter.
  • FIG. 17 illustrates the header in more detail in two side views taken at 90 degrees apart. As illustrated in the detail header view of FIG. 17, the thickness or dimension across a header 110/114 is about 6mm.
  • the inlet header 110, outlet header 114, and housing 1 ( 42 may all be of substantially similar thickness. As shown in FIG.
  • the thickness of the inlet header 110, outlet header 114, and housing 142 is about 6 mm. In another exemplary embodiment the thickness may be 8 mm, 10 mm, 12 mm or such other thickness as may be desirable.
  • Finite element analysis was performed on a device with features substantially similar to those in the embodiments shown in FIGS. 9-12, 16 and 17.
  • FIGS. 13 and 14 are based on the device used in the finite element analysis. The finite element analysis was performed using finite element analysis software from Adina R&D, Inc. and computer aided design drawings produced using software from
  • FIG. 18 shows the velocity of fluid flow through a device that does not include neck regions.
  • the fluid flow through the embodiment exhibits some non- uniform flow through the hollow'fibers of the embodiment, especially the hollow fibers closest to the inlet conduit 116 of the inlet header 110 and the outlet conduit 124 of the outlet header 114.
  • Non-uniform flow can result in increased shear forces in the fluid and stagnation points.
  • Approximate fluid flow velocities for this exemplary device are indicated at various points in the device in FIG. 18.
  • FIG. 19 shows the velocity of fluid flow through a device that includes neck regions.
  • the fluid flow through the device shows significantly reduced non-uniform flow through the hollow fibers of the embodiment as compared to the fluid flow shown in FIG. 18.
  • FIG. 20 shows the velocity of the fluid flow through the portion of the embodiment that includes neck regions and is most susceptible to stagnation points and shear forces in fluid.
  • the velocity and direction of fluid flow are depicted using directional arrows. The longer and larger the arrows the faster the fluid is flowing, and conversely the shorter and smaller the arrows the slower the fluid is moving.
  • the arrows in FIG. 20 show uniform fluid flow and no stagnation points in the fluid flow.
  • FIG. 21 is a graph of the results of the finite element analysis described above showing the pressure drop in relation to blood flow rate over the entire embodiment and over portions of the embodiment, such portions including the hollow fibers 140, headers (inlet header llO and outlet header 114), and the grafts (graft 118 connected to the inlet header 110 and graft 126 connected to the outlet header 114).
  • a low pressure drop over the device is achieved. It is desirable to have a low pressure differential over an ultrafiltration device. The low pressure differential enables the device to be utilized without use of a pump, and therefore makes the device more suitable for implantation.
  • the pressure differential over the embodiment as shown in FIG. 21 is less than the typical pressure differential between a femoral artery and a femoral vein. Typically the femoral artery is approximately 120 mmHg and the femoral vein is at about
  • FIG. 22 is a graph showing shear forces on the y-axis and exposure time on the x-axis. This graph is derived from Colton, CK. and E.G. Lowrie, "Hemodialysis: Physical Principles and Technical Considerations," in "The Kidney”, 2nd ed., B.M. Brenner and F.C.
  • the lines on the graph indicate the threshold points above which thrombosis is more likely to occur in red blood cells and platelets. Also included on the graph are the results of finite element analysis as described above. Finite element analysis results for embodiments with sixteen and thirty-two hollow fibers 140 are shown on the graph. The results place these embodiments below the lines on the graph, indicating that thrombosis is not likely to occur in connection with the sixteen Snd thirty- two hollow fiber 140 embodiments.
  • Certain benefits may be achieved by using an implantable device rather than a non-implantable device.
  • an implantable device After implantation of the device, and after an initial healing period, there is a lower risk of bleeding, clotting and infection than with a non-implanted device.
  • the likelihood of infection is reduced because there is less opportunity for bacteria to gain access to the device or the area in which the device is implanted.
  • there is a lower likelihood of thrombosis because the blood flow through the device remains uninterrupted and there is no exposure to air.
  • patients receiving the implantable device will be able to have greater fluid intake because of the ability to remove excess fluid from the body. This, combined with the ability to urinate, can substantially increase the quality of life for the patient suffering from kidney disease or heart failure.

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Abstract

L'invention concerne un dispositif d'ultrafiltration et un procédé servant au retrait d'un fluide en excès chez des patients hypervolémiques et/ou au retrait de toxines dans le sang, y compris chez des patients souffrant d'une maladie soit rénale, soit cardiovasculaire. Un mode de réalisation du dispositif comprend un boîtier contenant de multiples membranes fibres creuses à alésage large connectées au système vasculaire du patient par l'intermédiaire d'un élément de connexion comprenant des éléments de chemin de fluide bifurqué pour canaliser physiologiquement l'écoulement de sang soit vers, soit à partir de chaque membrane fibres creuses du dispositif, un canal pour diriger le fluide retiré par le dispositif vers un contenant de collecte approprié ou la vessie du patient, et des organes de contrôle contrôlant un retrait excessif d'eau à partir du patient. Les dispositifs peuvent être soit portés de façon extracorporelle, soit implantés de façon chirurgicale afin de permettre un retrait de fluide continu avec une liberté ambulatoire.
EP07811487.3A 2006-08-24 2007-08-23 Dispositif servant à retirer du fluide à partir du sang chez un patient Not-in-force EP2054105B1 (fr)

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US83967706P 2006-08-24 2006-08-24
PCT/US2007/018636 WO2008024434A1 (fr) 2006-08-24 2007-08-23 Dispositif servant à retirer du fluide à partir du sang chez un patient

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EP (1) EP2054105B1 (fr)
JP (1) JP5368305B2 (fr)
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CN (1) CN101505811B (fr)
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CN101505811A (zh) 2009-08-12
KR101419682B1 (ko) 2014-07-17
US9138521B2 (en) 2015-09-22
US8241239B2 (en) 2012-08-14
AU2007288199A1 (en) 2008-02-28
CN101505811B (zh) 2012-05-23
JP2010501257A (ja) 2010-01-21
WO2008024434A8 (fr) 2008-05-15
JP5368305B2 (ja) 2013-12-18
US20090234266A1 (en) 2009-09-17
WO2008024434A1 (fr) 2008-02-28
CA2661221A1 (fr) 2008-02-28
US20120265118A1 (en) 2012-10-18
EP2054105B1 (fr) 2018-07-18
KR20090053836A (ko) 2009-05-27
CA2661221C (fr) 2014-03-18
AU2007288199B2 (en) 2010-08-26

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